EP4143159A1 - Herstellung von aromatischen carboxyamiden durch eine palladium-katalysierte carbonylierungsreaktion - Google Patents

Herstellung von aromatischen carboxyamiden durch eine palladium-katalysierte carbonylierungsreaktion

Info

Publication number
EP4143159A1
EP4143159A1 EP21730097.9A EP21730097A EP4143159A1 EP 4143159 A1 EP4143159 A1 EP 4143159A1 EP 21730097 A EP21730097 A EP 21730097A EP 4143159 A1 EP4143159 A1 EP 4143159A1
Authority
EP
European Patent Office
Prior art keywords
alkyl
bis
formula
compounds
phenyl
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Granted
Application number
EP21730097.9A
Other languages
English (en)
French (fr)
Other versions
EP4143159B1 (de
Inventor
Mathias SCHELWIES
Florian Vogt
Christopher Koradin
Rocco Paciello
Roland Goetz
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
BASF SE
Original Assignee
BASF SE
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by BASF SE filed Critical BASF SE
Publication of EP4143159A1 publication Critical patent/EP4143159A1/de
Application granted granted Critical
Publication of EP4143159B1 publication Critical patent/EP4143159B1/de
Active legal-status Critical Current
Anticipated expiration legal-status Critical

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C271/00—Derivatives of carbamic acids, i.e. compounds containing any of the groups, the nitrogen atom not being part of nitro or nitroso groups
    • C07C271/06—Esters of carbamic acids
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J31/00—Catalysts comprising hydrides, coordination complexes or organic compounds
    • B01J31/16—Catalysts comprising hydrides, coordination complexes or organic compounds containing coordination complexes
    • B01J31/24—Phosphines, i.e. phosphorus bonded to only carbon atoms, or to both carbon and hydrogen atoms, including e.g. sp2-hybridised phosphorus compounds such as phosphabenzene, phosphole or anionic phospholide ligands
    • B01J31/2404—Cyclic ligands, including e.g. non-condensed polycyclic ligands, the phosphine-P atom being a ring member or a substituent on the ring
    • B01J31/2409—Cyclic ligands, including e.g. non-condensed polycyclic ligands, the phosphine-P atom being a ring member or a substituent on the ring with more than one complexing phosphine-P atom
    • B01J31/2414—Cyclic ligands, including e.g. non-condensed polycyclic ligands, the phosphine-P atom being a ring member or a substituent on the ring with more than one complexing phosphine-P atom comprising aliphatic or saturated rings
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C231/00—Preparation of carboxylic acid amides
    • C07C231/10—Preparation of carboxylic acid amides from compounds not provided for in groups C07C231/02 - C07C231/08
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C253/00—Preparation of carboxylic acid nitriles
    • C07C253/30—Preparation of carboxylic acid nitriles by reactions not involving the formation of cyano groups
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D271/00—Heterocyclic compounds containing five-membered rings having two nitrogen atoms and one oxygen atom as the only ring hetero atoms
    • C07D271/02—Heterocyclic compounds containing five-membered rings having two nitrogen atoms and one oxygen atom as the only ring hetero atoms not condensed with other rings
    • C07D271/06—1,2,4-Oxadiazoles; Hydrogenated 1,2,4-oxadiazoles
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J2231/00—Catalytic reactions performed with catalysts classified in B01J31/00
    • B01J2231/40—Substitution reactions at carbon centres, e.g. C-C or C-X, i.e. carbon-hetero atom, cross-coupling, C-H activation or ring-opening reactions
    • B01J2231/42—Catalytic cross-coupling, i.e. connection of previously not connected C-atoms or C- and X-atoms without rearrangement
    • B01J2231/4277—C-X Cross-coupling, e.g. nucleophilic aromatic amination, alkoxylation or analogues
    • B01J2231/4288—C-X Cross-coupling, e.g. nucleophilic aromatic amination, alkoxylation or analogues using O nucleophiles, e.g. alcohols, carboxylates, esters
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J2531/00—Additional information regarding catalytic systems classified in B01J31/00
    • B01J2531/80—Complexes comprising metals of Group VIII as the central metal
    • B01J2531/82—Metals of the platinum group
    • B01J2531/824—Palladium

Definitions

  • the present invention relates to a process for the preparation of aromatic carboxyamides of formula I, which can be obtained by a palladium-catalyzed carbonylation reaction of aromatic chlorides of formula II, amines of formula III and carbon monoxide in the presence of 1,5,7- triazabi-cyclo[4.4.0]dec-5-ene (TBD).
  • TBD 1,5,7- triazabi-cyclo[4.4.0]dec-5-ene
  • the invention further relates to a process for the preparation of aryl-5-trifluoromethyl-1,2,4-oxadiazoles, which are known for controlling phytopathogenic fungi, as described in, for example, WO 2015/185485 or in WO 2017/211649.
  • WO 2009/144197 A1 discloses a method for producing aromatic and heteroaromatic carboxylic acids, carboxylic acid esters and carboxylic acid amides (carboxyamides).
  • carboxyamides starting from aniline and aromatic chlorides at 130-150°C and 15 bar (1500 kPa) in the presence of a palladium catalyst and 1.5 equivalents of a base, for example DBU, triethylamine and potassium carbonate (working examples 6-1 to 6-3).
  • a base for example DBU, triethylamine and potassium carbonate
  • TBD 1,5,7-Triazabicyclo[4.4.0]dec-5-ene
  • the process of the present invention provides a solution to these problems.
  • the process of the present invention is cost efficient as it allows to use considerably lower amounts of the palladium catalyst than with previously reported procedures.
  • Aryl is phenyl or a 5- or 6-membered aromatic heterocycle; wherein the ring member atoms of the aromatic heterocycle include besides carbon atoms 1, 2, 3, or 4 heteroatoms selected from N, O, and S as ring member atoms with the provision that the heterocycle cannot contain 2 contiguous atoms selected from O and S; and wherein Aryl is further unsubstituted or further substituted with additional n identical or different radicals R A ; wherein n is 0,1 , 2, 3, or 4;
  • R 1 is C 1 -C 6 -alkyl, C 1 -C 6 -alkoxy, C 3 -C 11 -cycloalkyl, C 3 -C 8 -cycloalkenyl, C 2 -C 6 -alkenyl, C 2 -C 6 - alkynyl, C 1 -C 6 -alkoxyimino-C 1 C 4 -alkyl, C 2 -C 6 -alkenyloxyimino-C 1 C 4 -alkyl, C 2 -C 6 - alkynyloxyimino-C 1 -C 1 -C 1 -C
  • R 1 and R 2 together with the nitrogen atom to which they are attached, form a saturated or partially unsaturated mono- or bicyclic 3- to 10-membered heterocycle, wherein the heterocycle includes beside one nitrogen atom and one or more carbon atoms no further heteroatoms or 1 , 2 or 3 further heteroatoms independently selected from N, O, and S as ring member atoms with the provision that the heterocycle cannot contain 2 contiguous atoms selected from O and S; and wherein the heterocycle is unsubstituted or substituted with 1 , 2, 3, 4, or up to the maximum possible number of identical or different groups R 1a ; wherein
  • R 1a is halogen, oxo, cyano, NO 2 , OH, SH, NH 2 , C 1 -C 6 -alkyl, C 1 -C 6 -haloalkyl, C 1 -C 6 -alkoxy, C 1 -C 6 -haloalkoxy, C 1 -C 6 -alkylthio, C 1 -C 6 -haloalkylthio,
  • R 2 is hydrogen, C 1 -C 6 -alkyl, C 2 -C 6 -alkenyl, C 2 -C 6 -alkynyl, C 1 -C 6 -alkoxy, C 3 -C 11 -cycloalkyl,
  • any of the aliphatic or cyclic groups in R 2 are unsubstituted or substituted with 1, 2, 3, or up to the maximum possible number of identical or different radicals selected from the group consisting of halogen, hydroxy, oxo, cyano, C 1 -C 6 -alkyl, C 1 -C 6 -alkoxy, and C 3 -C 11 - cycloalkyl; the process comprising reacting an aromatic chloride of formula II, wherein Aryl is as defined above for compounds of formula I, with carbon monoxide and an amine compound of formula III, wherein R 1 and R 2 are as defined above for compounds of the formula I; and wherein the reaction is carried out in the presence of a palladium-based catalyst,
  • the carbonylation reaction of the present invention proceeds in the presence of a palladium- based catalyst selected from at least one Pd(ll) compound or Pd(0) compound, or complexes which are obtained from Pd(ll) compounds or Pd(0) compounds by complexing with ligands, particularly phosphine ligands.
  • the palladium-based catalyst can be used either as a prefabricated complex or may be put together in situ combining the palladium compound and the ligands, or salts thereof.
  • Suitable palladium compounds or complexes are, for example, palladium(ll)-acetate, palladium(ll)-chloride, palladium(ll)-bromide, palladium(ll)-nitrate, palladium(ll)-acetylacetonate, palladium(0)-dibenzylidenacetone-complex, palladium(0)-tetrakis (triphenylphosphine), palladium(0)-Bis(tri-o-tolylphosphine), palladium(0)(DPEphos)dicarbonyl, palladium(ll)- (Bis(diphenylphosphino)ferrocene)dichloride, palladium(ll)-propionate, palladium(ll)-Bis(triphenylphosphine)dichloride, palladium(l l)-nitrate, palladium(ll)-Bis(acetonitrile)dichloride, palladium(ll)-Bis
  • the carbonylation reaction preferably proceeds in the presence of a suitable Pd(ll) compound or a Pd(0) compound that are complexed with ligands, especially monodentate or bidentate phosphine ligands.
  • Examples for preferred monodentate phosphines are trialkylphosphines, triarylphosphines, dialkylarylphosphines, alkyldiarylphoshines, cycloalkyldiarylphosphines, dicycloalkylarylphosphines, and tricycloalkylphosphines.
  • Other examples for preferred phosphines are triheterocyclylphosphines und trihetarylphosphines.
  • Examples for preferred trialkylphosphines are triethylphosphine, tri-n-butylphosphine, tri-tert-butylphosphine, tri-/so- propylphosphine, tribenzylphosphine.
  • Examples for preferred tricycloalkylphosphines are tri(cyclopentyl)phosphine, tri(cyclohexyl)phosphine.
  • triarylphosphines examples include triphenylphosphine, tri(p-tolyl)phosphine, tri(m-tolyl)phosphine, tri(o-tolyl)phosphine, tri(p- methoxyphenyl)phosphine, tri(p-dimethylaminophenyl)phosphine, tri-(sodium-meta- sulfonatophenyl)-phosphine, diphenyl(2-sulfonatophenyl)phosphine, tri(1-naphthyl)phosphine and diphenyl-2-pyridylphosphine.
  • preferred dialkylarylphosphines are dimethylphenylphosphine and di-tert-butylphenylphosphine.
  • Examples for preferred alkyldiarylphoshines are ethyldiphenylphosphine and isopropyldiphenylphosphine.
  • An example for a preferred cycloalkyldiarylphosphine is cyclohexyldiphenylphosphine.
  • An example for a preferred dicycloalkylarylphosphine is dicyclohexylphenylphosphine.
  • triarylphosphines are tri(o- methoxyphenyl)phosphine, tri(m-methoxyphenyl)phosphine, tri(p-fluorphenyl)phosphine, tri(m- fluorphenyl)phosphine, tri(o-fluorphenyl)phosphine, tri(p-chlorphenyl)phosphine, tri(m- chlorphenyl)phosphine, tri(pentafluorphenyl)-phosphine, tris(p-trifluormethylphenyl)phosphine, tri[3,5-bis(trifluormethyl)phenyl]-phosphine, diphenyl(o-methoxyphenyl)phosphine, diphenyl(o- methylphenyl)phosphine, tris(3,5-dimethylphenyl)phosphine, and tri-2-naphthylphosphine.
  • An example for a preferred trihetarylphoshine is tri(o-furyl)phosphine.
  • An example for a preferred trialkylphosphine is triisobutylphosphine.
  • An example for a preferred triheterocyclylphosphine is tris(1-pyrrolidinyl)phosphine.
  • Particularly preferred are triphenylphosphine, di-tert-butylphenylphosphine, cyclohexyldiphenylphosphine, dicyclohexylphenylphosphine, tri(p-tolyl)phosphine and tri(cyclohexyl)phosphine.
  • Suitable bidentate phosphine ligands are 2,2'-Bis(diphenylphosphino)-1, 1'-binaphthyl (BINAP), 2-Bis(diphenylphosphino)ethane (DPPE), 1,3-Bis(diphenylphosphino)- propane (DPPP), 1,4-Bis(diphenylphosphino)butane (DPPB), 1, 1' -Bis(diphenylphos- phino)ferrocene (DPPF), 4,5-Bis(diphenylphosphino)-9,9-dimethylxanthene (Xantphos), Bis( 2- diphenylphosphino)phenyl] ether (DPEphos),1,2-Bis(di-tert-butylphosphinomethyl)benzene, 1,2-Bis(di-tert-pentylphosphinomethyl)- benzene, 1 ,2-Bis(di
  • the carbonylation reaction is carried out in the presence of a bidentate phosphine ligand; particularly DCPP.
  • the carbonylation reaction is carried out in the presence of free phosphine, which means that the phosphine is used in excess so that part of it is not bound in the palladium- complex.
  • the molar ratio of the phosphine ligand to palladium is typically between 0.5:1 to 10:1, preferably between 0.5:1 to 5:1.
  • the palladium-catalyst is used in an amount of less than 2 mol%, or less than 1 mol%, or less than 0.5 mol%, preferably between 0.001 to 0.3 mol%, more preferably between 0.001 to 0.2 mol%, based on the amount of the aromatic chloride of formula II.
  • the Pd-catalyst can undergo ligand exchange reactions so that the anionic ligands X and/or neutral Ligands L are replaced by other ligands, present in the reaction mixture, such as CO, amines or even parts of the substrate molecule (that can form complexes in significant amounts after elementary reactions such as oxidative addition or the arylhalide).
  • ligand exchange reactions so that the anionic ligands X and/or neutral Ligands L are replaced by other ligands, present in the reaction mixture, such as CO, amines or even parts of the substrate molecule (that can form complexes in significant amounts after elementary reactions such as oxidative addition or the arylhalide).
  • the palladium catalyst can be employed in homogenous solutions in the reaction medium or it may be formed from a heterogeneous catalyst precursor, for example colloidal Pd(0), Pd(0) applied to carrier materials, or Pd(ll) compounds applied to carrier materials, for example Pd(0) or Pd(ll) salts.
  • Suitable carrier materials are for example inorganic metal oxides, silicates and carbon.
  • the palladium catalysts can be removed from the reaction mixture using conventional workup procedures that are known to the skilled person and, after isolation, can be used again in carbonylation reactions of the type described herein.
  • the Pd-catalyst can be reused.
  • TBD*HCI can be removed from the resulting reaction mixture by filtration, then the solvent can be removed by distillation, followed by product separation by filtration or distillation.
  • the remaining residue contains most of the Palladium-catalyst that can be reused for a subsequent amino carbonylation reaction. All operations have to be carried out in a way not influencing catalyst performance, i.e. handling under inert atmosphere can be necessary.
  • the carbonylation reaction of the present invention is conducted in the presence of carbon monoxide.
  • This can mean that the reaction is carried out with pure carbon monoxide, or with mixtures of carbon monoxide with an inert gas, for example nitrogen or noble gases (helium, neon, argon).
  • the carbonylation is typically carried out at atmospheric pressure or at elevated pressure in the reaction vessel.
  • elevated pressure in the context of the present invention means a pressure above 1 bar (100 kPa).
  • Suitable reaction vessels or reactors are known to the person skilled in the art, for example from “Ullmanns Enzyklopadie der ischen Chemie, Vol. 1, 3 rd Edition, 1951, p. 769 ff.“.
  • the partial pressure of carbon monoxide in a carbonylation according to the present invention is less than 100 bar (10000 kPa), preferably less than 50 bar (5000 kPa), more preferably less than 20 bar (2000 kPa), and, in a particularly preferred aspect, less than 15 bar (1500 kPa).
  • the partial pressure of carbon monoxide varies in the range between 0.1 and 200 bar (100 and 20000 kPa), between 1 and 100 bar (100 and 10000 kPa), between 1 and 50 bar (100 and 5000 kPa), between 2 and 20 bar (200 and 2000 kPa), or between 5 and 15 bar (500 and 1500 kPa).
  • the carbonylation reaction is carried out in the absence of, or with reduced amounts of oxygen or air.
  • the carbonylation when carried out in a batchwise manner, requires batch times of from 1 hour to 100 hours, 2 hours to 50 hours, or 5 hours to 20 hours for a complete conversion of the aromatic chloride.
  • the temperature of the carbonylation reaction is suitably chosen in the range between 20°C and 200°C; preferably in the range between 50°C and 180°C; more preferably in the range between 50°C and 150°C; particularly in the range between 100°C and 140°C.
  • the carbonylation is carried out at a temperature in the range between 50 and 180°C and at a partial pressure of carbon monoxide in the range between 1 and 100 bar (100 and 5.000 kPa).
  • the carbonylation reaction of the present invention is carried out at a temperature in the range between 50°C and 150°C and at a partial pressure of carbon monoxide in the range between 2 and 20 bar (200 and 2.000 kPa).
  • the carbonylation reaction of the present invention is carried out at a temperature in the range between 100°C and 140°C and at a partial pressure of carbon monoxide in the range between 5 and 15 bar (500 and 1500 kPa).
  • the carbonylation reaction of the present invention is carried out in the presence of an inert solvent.
  • suitable solvents are, for example, aliphatic, cycloaliphatic and aromatic hydrocarbons (pentane, hexane, petroleum ether, cyclohexane, methylcyclohexane, benzene, toluene, xylene), aliphatic halogen-hydrocarbons (methylene chloride, chloroform, di- and tetrachloroethane), nitriles (acetonitrile, propionitrile, benzonitrile), ethers (diethylether, dibutylether, tert-butylmethylether, ethylene glycol dimethyl ether, ethylene glycol, diethyl ether, diethylene glycol dimethyl ether, 2-methyltetrahydrofuran, tetrahydrofuran, dioxane, diethylene, glycol monomethyl- or monoethyl ether),
  • TBD is used in an amount of at least 30 mol% based on the amount of the compound of formula II, or at least 80 mol%, or at least 100 mol%. In another aspect of the present invention TBD is used in an amount that ranges between 30 mol% and 1000 mol% based on the amount of the compound of formula II.
  • TBD is used in an amount that ranges between 50 mol% and 200 mol% based on the amount of the compound of formula II. In yet another aspect TBD is used in an amount that ranges between 80 mol% and 130 mol% based on the amount of the compound of formula II.
  • the carbonylation reaction of the present invention may be carried out, in addition to TBD, in the presence of an inorganic base b1.
  • inorganic bases b1 are alkali metal and alkaline earth metal carbonates, hydroxides and phosphates, which provide the advantage that they are not expensive, convenient to handle and an aqueous workup allows for their easy removal after the carbonylation reaction is finished.
  • Preferred alkali metal carbonates are sodium and potassium carbonate, particularly potassium carbonate.
  • Preferred alkaline earth metal carbonates are magnesium and calcium carbonates.
  • Preferred alkali metal phosphates are trisodium phosphate (Na 3 PO 4 ) and disodium phosphate (Na 3 HPO 4 ).
  • the molar ratio of compound of formula III to compound of formula II is typically between 1 :1 to 10:1 , preferably between 1 :1 to 5: 1 , more preferably between 1 :1 to 2: 1.
  • the aromatic chloride used in the carbonylation process is of formula 11. a, wherein n is 0 or 1 ; A 1 and A 2 are independently selected from nitrogen, C-H, or C-R A ; and wherein no more than one of A 1 and A 2 is nitrogen; and wherein R A is as defined or preferably defined herein for compounds of formula I, to obtain an aromatic carboxyamide of formula I. a, wherein the variables n, R A , A 1 , and A 2 have the meaning as defined for compounds 11. a and wherein the variables R 1 and R 2 have the meaning as defined for compounds of formula I.
  • the aromatic chloride used in the carbonylation process is of formula II. b, wherein n is 0 or 1 and R A is as defined or preferably defined herein for compounds of formula I, to obtain an aromatic carboxyamide of formula l.b, wherein the variables n and R A have the meaning as defined for compounds II. b and wherein the variables R 1 and R 2 have the meaning as defined or preferably defined herein for compounds of formula I.
  • variable A is phenyl in compounds of formula I.
  • variable n is 1 and R A is fluorine in compounds of formula I, I. a, l.b, II, II. a, and II. b.
  • variable n is 0 in compounds of formula I, I. a, l.b, II, II. a, and II. b.
  • One embodiment relates to the preparation of compounds of formulae I, III, l.a and l.b, IV, V, and VI, wherein R 1 is methyl, ethyl, n-propyl, iso-propyl, n-butyl, sec-butyl, iso-butyl, cyclopropyl, 2-methoxyiminoethyl, bicyclo[1.1.1]pentan-1-yl, or phenyl; and wherein the phenyl group is unsubstituted or substituted with 1, 2, 3 or up to the maximum possible number of identical or different radicals selected from the group consisting of fluorine, chlorine, cyano, methyl, ethyl, methoxy, trifluoromethyl, trifluoromethoxy, difluoromethyl, difluoromethoxy, and cyclopropyl; and R 2 is hydrogen, methyl, or ethyl.
  • Another embodiment relates to the preparation of compounds of formulae I, III, l.a and l.b, IV, V, and VI, wherein R 1 is methyl or phenyl, wherein the phenyl ring is unsubstituted or substituted with 1, 2, 3, or 4 identical or different groups selected from halogen; and wherein R 2 is hydrogen, methyl, or ethyl.
  • a further embodiment relates to the preparation of compounds of formulae I, III, I. a and l.b, IV,
  • R 1 is methyl, 2-methoxyiminoethyl, bicyclo[1.1.1]pentan-1-yl, 2-fluoro-phenyl, 4-fluoro-phenyl, or 2-difluoromethoxy-phenyl; and R 2 is hydrogen.
  • Yet another embodiment relates to the preparation of compounds of formulae I, III, I. a and l.b,
  • R 1 is methyl, 2-fluoro-phenyl, 4-fluoro-phenyl, or 2,4-difluoro-phenyl; in particular methyl or 2-fluoro-phenyl; and wherein R 2 is hydrogen.
  • the carbonylation reaction is carried out at a temperature in the range between 100°C and 140°C and at a partial pressure of carbon monoxide in the range between 5 and 15 bar (500 and 1500 kPa).
  • Embodiment E.2 is based on embodiment E.1 , whereas the reaction is carried out in the presence of a palladium-catalyst in an amount of less than 2 mol%, based on the amount of the compound of formula II; and wherein at least one organic mono- or bidentate phosphine ligand is used for the palladium-catalyst selected from the group consisting of triphenylphosphine, tri(tolyl)phosphine, tri-n-butylphosphine, tricyclohexylphosphine, tri-iso-propylphosphine, tri-tert- butylphosphine, S-phos (2-dicyclohexylphosphino-2',6'-dimethoxybiphenyl), cyclohexyldiphenylphosphine, triisopropylphosphine, phenyldicycloheylphosphine, butyldiadam
  • Embodiment E.4 is based on embodiment E.3, wherein the solvent is tetrahydrofuran, dimethylformamide, N-methylpyrrolidone, dioxane, 2-methyltetrahydrofuran, N,N- dimethylacetamide, toluene, or acetonitrile.
  • Embodiment E.5 is based on embodiment E.4, whereas TBD is used in an amount of at least 80 mol% based on the amount of the compound of formula II.
  • Embodiment E.6 is based on embodiment E.4, whereas TBD is used in an amount that ranges between 80 mol% and 130 mol% based on the amount of the compound of formula II.
  • Embodiment E.6: is based on embodiment E.5 or E.6, wherein the process relates to the preparation of compounds of formulae l.b, IV, V, and VI, wherein R 1 is methyl or 2-fluoro-phenyl; and wherein R 2 is hydrogen.
  • Compounds of formula l.b can be further transformed to obtain compounds of formula IV, wherein the variables R A , n, R 1 and R 2 are as defined or preferably defined herein.
  • Compounds IV are valuable chemical intermediates for the synthesis of 3-aryl-5-trifluoromethyl-1 ,2,4- oxadiazoles, which are known to be useful for controlling phytopathogenic fungi.
  • compounds of formula IV can be obtained by treatment of compounds of formula l.b with hydroxylamine or a salt thereof, for example the hydrochloride salt, in the presence of a base, preferably triethylamine, sodium hydroxide or sodium methylate, in a suitable solvent, such as methanol, ethanol or water, or a mixture of these solvents, at a temperature between 0°C and 100°C.
  • a base preferably triethylamine, sodium hydroxide or sodium methylate
  • a suitable solvent such as methanol, ethanol or water, or a mixture of these solvents
  • the preparation of fungicidal 3-aryl-5-trifluoromethyl-1 ,2,4-oxadiazoles involves the formation of the oxadiazole ring through the reaction of hydroxyamidine compounds of formula IV with an activated derivative of trifluoroacetic acid. Accordingly, in a further embodiment of the present invention, the compound of formula IV is reacted with an activated species of trifluoroacetic acid to obtain a compound of formula V, wherein the variables R A , n, R 1 and R 2 are as defined or preferably defined herein.
  • Another embodiment of the present invention relates to the process further comprising the step of reacting the compound of formula V to obtain a compound of formula VI, wherein the variables R A , n, R 1 and R 2 are as defined or preferably defined herein.
  • Compounds of formula VI can be prepared from compounds of formula V through treatment with Lawesson’s reagent or phosphorus pentasulfide in an inert organic solvent, such as non- halogenated aliphatic hydrocarbons, non-halogenated cycloaliphatic hydrocarbons, halogenated aliphatic hydrocarbons, halogenated aromatic hydrocarbons, amides, ethers, esters, ketones, nitriles; for example toluene, tetrahydrofuran, dioxane or ethyl acetate; at a temperature between 0°C and 130°C, preferentially between 60°C and 80°C.
  • Lawesson’s reagent or phosphorus pentasulfide in an inert organic solvent such as non- halogenated aliphatic hydrocarbons, non-halogenated cycloaliphatic hydrocarbons, halogenated aliphatic hydrocarbons, halogenated aromatic hydrocarbon
  • the present invention relates to the preparation of compounds V.a, V.b and VI. a.
  • C n -C m indicates the number of carbon atoms possible in each case in the substituent or substituent moiety in question.
  • halogen refers to fluorine, chlorine, bromine and iodine.
  • C 1 C 6 -alkyl refers to a straight-chained or branched saturated hydrocarbon group having 1 to 6 carbon atoms, for example methyl, ethyl, propyl, 1-methylethyl, butyl, 1- methylpropyl, 2-methylpropyl, and 1 ,1-dimethylethyl.
  • C 2 -C 6 -alkenyl refers to a straight-chain or branched unsaturated hydrocarbon radical having 2 to 6 carbon atoms and a double bond in any position, such as ethenyl, 1-propenyl, 2- propenyl (allyl), 1-methylethenyl, 1-butenyl, 2-butenyl, 3-butenyl, 1-methyl-1-propenyl, 2-methyl-
  • C 2 -C 6 -alkynyl refers to a straight-chain or branched unsaturated hydrocarbon radical having 2 to 6 carbon atoms and containing at least one triple bond, such as ethynyl, 1-propynyl,
  • 2-propynyl (propargyl), 1-butynyl, 2-butynyl, 3-butynyl, 1-methyl-2-propynyl.
  • C 1 -C 6 -haloalkyl refers to a straight-chained or branched alkyl group having 1 to 6 carbon atoms (as defined above), wherein some or all of the hydrogen atoms in these groups may be replaced by halogen atoms as mentioned above, for example chloromethyl, bromomethyl, dichloromethyl, trichloromethyl, fluoromethyl, difluoromethyl, trifluoromethyl, chlorofluoromethyl, dichlorofluoromethyl, chlorodifluoromethyl, 1-chloroethyl, 1-bromoethyl, 1- fluoroethyl, 2-fluoroethyl, 2,2-difluoroethyl, 2,2,2-trifluoroethyl, 2-chloro-2-fluoroethyl, 2-chloro- 2,2-difluoroethyl, 2,2-dichloro-2-fluoroethyl, 2,2,2-tri chloroe
  • C 1 -C 6 -alkoxy refers to a straight-chain or branched alkyl group having 1 to 6 carbon atoms (as defined above) which is bonded via an oxygen, at any position in the alkyl group, for example methoxy, ethoxy, n-propoxy, 1-methylethoxy, butoxy, 1-methylpropoxy, 2- methylpropoxy or 1,1-dimethylethoxy.
  • C 1 -C 6 -haloalkoxy refers to a C 1 -C 6 -alkoxy group as defined above, wherein some or all of the hydrogen atoms may be replaced by halogen atoms as mentioned above, for example, OCH 2 F, OCHF 2 , OCF 3 , OCH 2 CI, OCHCI 2 , OCCI 3 , chlorofluoromethoxy, dichlorofluoromethoxy, chlorodifluoromethoxy, 2-fluoroethoxy, 2-chloroethoxy, 2-bromoethoxy, 2-iodoethoxy, 2,2- difluoroethoxy, 2,2,2-trifluoroethoxy, 2-chloro-2-fluoroethoxy, 2-chloro-2,2-difluoroethoxy, 2,2- dichloro-2-fluoroethoxy, 2,2,2-trichloroethoxy, OC2F5, 2-fluoropropoxy, 3-fluoropropoxy, 2,
  • phenyl-C 1 -C 4 -alkyl or heteroaryl-C 1 -C 4 -alkyl refer to alkyl having 1 to 4 carbon atoms (as defined above), wherein one hydrogen atom of the alkyl radical is replaced by a phenyl or hetereoaryl radical respectively.
  • C 1 -C 4 -alkoxy-C 1 -C 4 -alkyl refers to alkyl having 1 to 4 carbon atoms (as defined above), wherein one hydrogen atom of the alkyl radical is replaced by a C 1 -C 4 -alkoxy group (as defined above).
  • Ci-C4-alkylthio-CrC4-alkyl refers to alkyl having 1 to 4 carbon atoms (as defined above), wherein one hydrogen atom of the alkyl radical is replaced by a C 1 -C 4 -alkylthio group.
  • C 1 -C 6 -alkylthio refers to straight-chain or branched alkyl groups having 1 to 6 carbon atoms (as defined above) bonded via a sulfur atom.
  • C 1 -C 6 -haloalkylthio refers to straight-chain or branched haloalkyl group having 1 to 6 carbon atoms (as defined above) bonded through a sulfur atom, at any position in the haloalkyl group.
  • hydroxyC 1 -C 4 -alkyl refers to alkyl having 1 to 4 carbon atoms, wherein one hydrogen atom of the alkyl radical is replaced by a OH group.
  • aminoC 1 -C 4 -alkyl refers to alkyl having 1 to 4 carbon atoms, wherein one hydrogen atom of the alkyl radical is replaced by a NH 2 group.
  • C 1 -C 6 -alkylamino refers to an amino group, which is substituted with one residue independently selected from the group that is defined by the term C 1 -C 6 -alkyl.
  • diC 1 -C 6 -alkylamino refers to an amino group, which is substituted with two residues independently selected from the group that is defined by the term C 1 -C 6 -alkyl.
  • C 1 -C 4 -alkylamino-C 1 -C 4 -alkyl refers to refers to alkyl having 1 to 4 carbon atoms (as defined above), wherein one hydrogen atom of the alkyl radical is replaced by a C 1 -C 4 -alkyl-NH- group which is bound through the nitrogen.
  • diC 1 -C 4 -alkylamino-C 1 -C 4 -alkyl refers to refers to alkyl having 1 to 4 carbon atoms (as defined above), wherein one hydrogen atom of the alkyl radical is replaced by a (C 1 -C 4 -alkyl) 2 N- group which is bound through the nitrogen.
  • C 2 -C 6 -alkenyl refers to a straight-chain or branched unsaturated hydrocarbon radical having 2 to 6 carbon atoms and a double bond in any position, such as ethenyl, 1-propenyl, 2- propenyl (allyl), 1-methylethenyl, 1-butenyl, 2-butenyl, 3-butenyl, 1-methyl-1-propenyl, 2-methyl-
  • C 2 -C 6 -alkynyl refers to a straight-chain or branched unsaturated hydrocarbon radical having 2 to 6 carbon atoms and containing at least one triple bond, such as ethynyl, 1-propynyl,
  • 2-propynyl (propargyl), 1-butynyl, 2-butynyl, 3-butynyl, 1-methyl-2-propynyl.
  • C 3 -C 11 -cycloalkyl refers to a monocyclic, bicyclic or tricyclic saturated univalent hydrocarbon radical having 3 to 11 carbon ring members that is connected through one of the ring carbon atoms by substitution of one hydrogen atom, such as cyclopropyl (C 3 H 5 ), cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, cyclooctyl, bicyclo[1.1.0]butyl, bicyclo[2.1.0]pentyl, bicyclo[1.1.1]pentyl, bicyclo[3.1.0]hexyl, bicyclo[2.1.1]hexyl, norcaranyl (bicyclo[4.1.0]heptyl) and norbornyl (bicyclo[2.2.1]heptyl).
  • C 3 -C 11 -cycloalkyl-C 1 -C 6 -alkyl refers to alkyl having 1 to 11 carbon atoms, wherein one hydrogen atom of the alkyl radical is replaced by a C 3 -C 11 -cycloalkyl group as defined above.
  • C 3 -C 11 -cycloalkoxy refers to a cyclic univalent hydrocarbon radical having 3 to 11 carbon ring members (as defined above) that is bonded via an oxygen, at any position in the cycloalkyl group, for example cyclopropyloxy.
  • aliphatic refers to compounds or radicals composed of carbon and hydrogen and which are non-aromatic compounds.
  • An “alicyclic” compound or radical is an organic compound that is both aliphatic and cyclic. They contain one or more all-carbon rings which may be either saturated or unsaturated, but do not have aromatic character.
  • cyclic moiety or “cyclic group” refer to a radical which is an alicyclic ring or an aromatic ring, such as, for example, phenyl or heteroaryl.
  • any of the aliphatic or cyclic groups are unsubstituted or substituted with...” refers to aliphatic groups, cyclic groups and groups, which contain an aliphatic and a cyclic moiety in one group, such as in, for example, C 3 -C 8 -cycloalkyl-C 1 -C 4 -alkyl; therefore a group which contains an aliphatic and a cyclic moiety both of these moieties may be substituted or unsubstituted independently of each other.
  • phenyl refers to an aromatic ring systems incuding six carbon atoms (commonly referred to as benzene ring.
  • heteroaryl refers to aromatic monocyclic or polycyclic ring systems incuding besides carbon atoms, 1, 2, 3 or 4 heteroatoms independently selected from the group consisting of N,
  • saturated 3- to 7-membered carbocycle is to be understood as meaning monocyclic saturated carbocycles having 3, 4 or 5 carbon ring members. Examples include cyclopropyl, cyclopentyl, cyclohexyl, cycloheptyl, and the like.
  • 3- to 10-membered saturated, partially unsaturated or aromatic mono- or bicyclic heterocycle wherein the ring member atoms of said mono- or bicyclic heterocycle include besides carbon atoms further 1 , 2, 3 or 4 heteroatoms selected from N, O and S as ring member atoms
  • a 3- or 4-membered saturated heterocycle which contains 1 or 2 heteroatoms from the group consisting of N, O and S as ring members such as oxirane, aziridine, thiirane, oxetane, azetidine, thiethane, [1,2]dioxetane, [1,2]dithietane, [1,2]diazetidine
  • a 5- or 6-membered saturated or partially unsaturated heterocycle which contains 1, 2 or 3 heteroatoms from the group consisting
  • 5- or 6-membered heteroaryl or the term ”5- or 6-membered aromatic heterocycle” refer to aromatic ring systems incuding besides carbon atoms, 1, 2, 3 or 4 heteroatoms independently selected from the group consisting of N, O and S, for example, a 5-membered heteroaryl such as pyrrol-1 -yl, pyrrol-2-yl, pyrrol-3-yl, thien-2-yl, thien-3-yl, furan-2-yl, furan-3-yl, pyrazol-1-yl, pyrazol-3-yl, pyrazol-4-yl, pyrazol-5-yl, imidazol-1-yl, imidazol-2-yl, imidazol-4-yl, imidazol-5-yl, oxazol-2-yl, oxazol-4-yl, oxazol-5-yl, isoxazol-3-yl, isoxazol
  • Table 1 provides the results of experiments with variations to the reaction conditions of Example 1 above. [Comment on results]
  • Examples 1.3 to 1.5 of Table 1 represent comparative examples showing that at the chosen conditions (at low catalyst loadings of 0.25 mol% Pd), the reaction with TBD proceeds much faster after 20 h reaction compared to the case when TBD is replaced by an equimolar amount of another base.
  • Table 1 a ) identical with example 1 above; b ) example representing the present invention, identical with example 1 unless otherwise mentioned in table 1 c ) comparative example not according to the invention, identical with example 1 unless otherwise mentioned in table 1
  • Example 2 Preparation of N , N-diethyl-3,5-dimethyl-benzamide Palladium(ll)chloride (57 mg, 0.32mmol, 4 mol%), 1,3-Bis(dicyclohexylphosphino)propane bis(tetrafluoroborate) (197 mg, 0.32 mmol, 4 mol%), TBD (1.1 g, 8.0 mmol) and 5-Chlor-m-xylol (1,13 g, 8,0 mmol) were kept under argon in an autoclave.
  • Example 2 of Table 2 represents reaction conditions (using a different aryl halide / amine combination compared to table 1) according to the present invention, as the reaction is carried out using TBD as base.
  • Example 2.1 is a comparative example not representing the invention. Also in this case the reaction with TBD proceeds faster after 20 h reaction time compared to the case when TBD is replaced by an equimolar amount of potassium carbonate.
  • Table 2 a ) example representing the present invention, identical with example 2 unless otherwise mentioned in table 2; b ) comparative example not according to the invention; carried out as example 2, TBD was replaced with potassium carbonate.
  • Example 3 of Table 3 represents reaction conditions (using a different aryl halide / amine combination compared to table 1) according to the present invention, as the reaction is carried out using TBD as base.
  • Example 3.1 is a comparative example not representing the invention.
  • the reaction with TBD proceeds much faster after 20 h reaction time compared to the case when TBD is replaced by an equimolar amount of potassium carbonate.
  • Table 3 a ) identical with example 3 above; b ) comparative example not according to the invention; TBD was replaced with potassium carbonate.

Landscapes

  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Inorganic Chemistry (AREA)
  • Engineering & Computer Science (AREA)
  • Materials Engineering (AREA)
  • Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
EP21730097.9A 2020-04-29 2021-04-19 Herstellung von aromatischen carboxamiden durch eine palladium-katalysierte carbonylierungsreaktion Active EP4143159B1 (de)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
EP20172095 2020-04-29
PCT/EP2021/060119 WO2021219424A1 (en) 2020-04-29 2021-04-19 Preparation of aromatic carboxyamides by a palladium-catalyzed carbonylation reaction

Publications (2)

Publication Number Publication Date
EP4143159A1 true EP4143159A1 (de) 2023-03-08
EP4143159B1 EP4143159B1 (de) 2024-04-10

Family

ID=70480113

Family Applications (1)

Application Number Title Priority Date Filing Date
EP21730097.9A Active EP4143159B1 (de) 2020-04-29 2021-04-19 Herstellung von aromatischen carboxamiden durch eine palladium-katalysierte carbonylierungsreaktion

Country Status (4)

Country Link
US (1) US20230339847A1 (de)
EP (1) EP4143159B1 (de)
CN (1) CN115315419A (de)
WO (1) WO2021219424A1 (de)

Family Cites Families (17)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4128554A (en) 1974-05-10 1978-12-05 University Of Delaware Process for the preparation of carboxylic acid amides from organic halides
US3988358A (en) 1974-05-10 1976-10-26 The University Of Delaware Process for the preparation of carboxylic acid esters from organic halides
US5672750A (en) 1994-12-16 1997-09-30 Eastman Chemical Company Preparation of aromatic amides from carbon monoxide, an amine and an aromatic chloride
CA2608718A1 (en) 2005-05-18 2006-11-23 Pfizer Limited 1, 2, 4-triazole derivatives as vasopressin antagonists
WO2009144197A1 (de) 2008-05-27 2009-12-03 Basf Se Verfahren zur herstellung von aromatischen und heteroaromatischen carbonsäuren, carbonsäureestern und carbonsäureamiden
TW201038580A (en) 2009-02-02 2010-11-01 Pfizer 4-amino-5-oxo-7,8-dihydropyrimido[5,4-f][1,4]oxazepin-6(5H)-yl)phenyl derivatives
BR112013018228A2 (pt) * 2011-01-28 2016-11-08 Du Pont “métodos para preparar um composto de fórmula 1 e método para preparar um composto de fórmula 5"
AU2014236812B2 (en) 2013-03-14 2018-03-01 Amgen Inc. Heteroaryl acid morpholinone compounds as MDM2 inhibitors for the treatment of cancer
BR122021017872B1 (pt) 2014-06-06 2021-11-23 Basf Se Uso dos compostos, composição agroquímica e método para o combate dos fungos fitopatogênicos
EP3458446A1 (de) 2016-05-20 2019-03-27 Syngenta Participations AG Mikrobiozide oxadiazolderivate
JP2019523224A (ja) 2016-06-03 2019-08-22 シンジェンタ パーティシペーションズ アーゲー 殺微生物オキサジアゾール誘導体
BR112018074253B1 (pt) 2016-06-09 2022-08-30 Basf Se Compostos, composição agroquímica, uso dos compostos e método para combater fungos nocivos fitopatogênicos
WO2017211652A1 (en) 2016-06-09 2017-12-14 Basf Se Substituted oxadiazoles for combating phytopathogenic fungi
AR108745A1 (es) 2016-06-21 2018-09-19 Syngenta Participations Ag Derivados de oxadiazol microbiocidas
DK3522715T3 (da) 2016-10-06 2021-04-12 Syngenta Participations Ag Mikrobiocide oxadiazolderivativer
BR112020001211B1 (pt) 2017-07-28 2023-05-16 Basf Se Processo para preparar compostos de fórmula i
CN109867284B (zh) 2017-12-01 2022-10-25 嘉兴学院 一种可现场释放一氧化碳的试剂及其制备和应用

Also Published As

Publication number Publication date
EP4143159B1 (de) 2024-04-10
WO2021219424A1 (en) 2021-11-04
CN115315419A (zh) 2022-11-08
US20230339847A1 (en) 2023-10-26

Similar Documents

Publication Publication Date Title
KR102573454B1 (ko) 치환 3-아릴-5-트리플루오로메틸-1,2,4-옥사디아졸의 제조
EP4103555B1 (de) Herstellung von aromatischen carbonylverbindungen durch katalytische oxidation mit molekularem sauerstoff
EP4143158A1 (de) Herstellung von aromatischen carboxyamiden durch palladiumkatalysierte carbonylierungsreaktion
EP4143159B1 (de) Herstellung von aromatischen carboxamiden durch eine palladium-katalysierte carbonylierungsreaktion
EP4100397B1 (de) Herstellung von substituierten 3-aryl-5-trifluormethyl-1,2,4-oxadiazolen
EP4100396B1 (de) Herstellung von substituierten 3-aryl-5-trifluormethyl-1,2,4-oxadiazolen
US20230127884A1 (en) A process for the preparation of 4-cyanobenzoyl chlorides
KR20240033027A (ko) 치환된 아미독심의 제조
WO2024110227A1 (en) Preparation of 4-cyanobenzoyl chlorides from alkali metal 4-carbamoyl-benzoates
CN117597330A (zh) 取代的偕胺肟的制备
US20230028964A1 (en) Preparation of substituted aromatic carboxamides
EP4370509A1 (de) Verfahren zur herstellung von alkyltrifluoracetaten
IL298517A (en) Preparation of 4-(n'-hydroxycarbamimidoyl)substituted benzoic acids

Legal Events

Date Code Title Description
STAA Information on the status of an ep patent application or granted ep patent

Free format text: STATUS: UNKNOWN

STAA Information on the status of an ep patent application or granted ep patent

Free format text: STATUS: THE INTERNATIONAL PUBLICATION HAS BEEN MADE

PUAI Public reference made under article 153(3) epc to a published international application that has entered the european phase

Free format text: ORIGINAL CODE: 0009012

STAA Information on the status of an ep patent application or granted ep patent

Free format text: STATUS: REQUEST FOR EXAMINATION WAS MADE

17P Request for examination filed

Effective date: 20221129

AK Designated contracting states

Kind code of ref document: A1

Designated state(s): AL AT BE BG CH CY CZ DE DK EE ES FI FR GB GR HR HU IE IS IT LI LT LU LV MC MK MT NL NO PL PT RO RS SE SI SK SM TR

DAV Request for validation of the european patent (deleted)
DAX Request for extension of the european patent (deleted)
GRAP Despatch of communication of intention to grant a patent

Free format text: ORIGINAL CODE: EPIDOSNIGR1

STAA Information on the status of an ep patent application or granted ep patent

Free format text: STATUS: GRANT OF PATENT IS INTENDED

INTG Intention to grant announced

Effective date: 20231129

P01 Opt-out of the competence of the unified patent court (upc) registered

Effective date: 20231220

GRAS Grant fee paid

Free format text: ORIGINAL CODE: EPIDOSNIGR3

GRAA (expected) grant

Free format text: ORIGINAL CODE: 0009210

STAA Information on the status of an ep patent application or granted ep patent

Free format text: STATUS: THE PATENT HAS BEEN GRANTED

AK Designated contracting states

Kind code of ref document: B1

Designated state(s): AL AT BE BG CH CY CZ DE DK EE ES FI FR GB GR HR HU IE IS IT LI LT LU LV MC MK MT NL NO PL PT RO RS SE SI SK SM TR

REG Reference to a national code

Ref country code: GB

Ref legal event code: FG4D

REG Reference to a national code

Ref country code: CH

Ref legal event code: EP

REG Reference to a national code

Ref country code: DE

Ref legal event code: R096

Ref document number: 602021011684

Country of ref document: DE

REG Reference to a national code

Ref country code: IE

Ref legal event code: FG4D